Survival in a Case of Emphysematous Cholecystitis With Sepsis Caused by Clostridium perfringens

A 77-year-old man presented to the Department of Internal Medicine with a chief complaint of abdominal pain. During the outpatient examination, a computed tomography (CT) scan showed gallstones. The patient developed worsening abdominal pain and fever and was admitted to the emergency department. He was diagnosed with cholecystitis and hospitalized. Treatment with antimicrobial agents was initiated. On the second day of hospitalization, the patient developed a fever of 39°C, hypotension, and oliguria. An emergency CT scan was performed, which showed gas production in the gallbladder. He was diagnosed with emphysematous cholecystitis, and emergency percutaneous transhepatic gallbladder drainage was performed. The patient was transferred to the high-care unit, and intensive care was initiated. On the eighth day, a follow-up CT scan showed an abscess in the gallbladder bed, and drainage was performed percutaneously. His general condition gradually improved, and he was discharged from the hospital on day 24. The patient was readmitted for cholecystectomy three months after the initial admission. The prognosis of sepsis caused by Clostridium perfringens is extremely poor, with a mortality rate of 70%-100%. We present a case of emphysematous cholecystitis successfully treated with multimodal treatment despite the presence of sepsis due to Clostridium perfringens and discuss the possible prognostic factors by reviewing the literature.


Introduction
Sepsis, a severe clinical condition with significant morbidity and mortality, is currently recognized as a substantial public health concern.The incidence of sepsis cases per year has been gradually increasing, potentially attributed to the aging population [1].Especially, sepsis caused by Clostridium perfringens has a high mortality rate and an extremely poor prognosis.In this report, we present a case of emphysematous cholecystitis with sepsis due to Clostridium perfringens, which was successfully treated with multimodal treatment, and discuss the possible prognostic factors by reviewing the literature.

Case Presentation
A 77-year-old male patient was admitted with a chief complaint of abdominal pain.His past medical history included stroke, diabetes mellitus, and hypertension.His family history was unremarkable.Nine days before admission, he visited the Internal Medicine Department of the hospital with a chief complaint of abdominal pain and was diagnosed with cholelithiasis.At that time, a thorough examination was planned to be conducted on an outpatient basis.Nine days later, he was admitted to the emergency department due to worsening abdominal pain and fever and was hospitalized with a diagnosis of cholecystitis.
On physical examination upon admission, the patient was awake, alert, and oriented to person, time, place, and events.Body temperature was 39.7°C, heart rate was 109 bpm, blood pressure was 140/81 mmHg, and SpO2 was 94%-96% (room air).Furthermore, physical examination revealed a flat and soft abdomen, spontaneous pain over the abdomen, and no tenderness.Laboratory tests upon admission revealed elevated white blood cell counts and C-reactive protein levels.The hepatobiliary enzyme and bilirubin levels were also elevated (Table 1).2).A CT scan on the same day showed a large gallstone of about 4 cm in length at the neck of the gallbladder, gallbladder swelling, and thickening of the gallbladder wall.Additionally, a gas image in the gallbladder wall and fluid accumulation with a gas image in the adjacent hepatic bed were observed.Based on these findings, the patient was diagnosed with emphysematous cholecystitis and liver abscess (Fig. 1).Emergency drainage was performed on the same day.Percutaneous transhepatic gallbladder drainage (PTGBD) was performed after puncturing the liver abscess and aspirating the abscess as much as possible (Fig. 2).At this time, Grampositive rods were detected in the blood culture taken the previous day.Specimen images of the anaerobic bottles showed large Gram-positive rods (Fig. 3).The culture bottles were filled with gas, suggesting a large amount of gas production.The patient was transferred to the high care unit (HCU) on the second day and treated with cefoperazone/sulbactam and clindamycin.Additionally, he received gammaglobulin for three days for severe infection.Culture results were obtained on the sixth day, and Clostridium perfringens were detected in blood, pus, and bile.Based on the sensitivity test results, the antimicrobial agent was changed to cefmetazole on the tenth day (Fig. 4).On the eighth day, a follow-up CT scan was performed, which showed fluid retention where there was originally a gas image of the liver abscess (Fig. 5).Therefore, percutaneous transhepatic abscess drainage (PTAD) was performed on the same day by puncture from the side of PTGBD (Fig. 6).Again, the abscess was sent for culture, but the culture was negative.On the 16th day, the PTAD was removed, and the PTGBD was removed on the 22nd day.The patient was discharged on the 27th day.Cholecystectomy was performed three months after admission, and subtotal cholecystectomy was performed due to severe inflammatory adhesion.Pathology revealed a diagnosis of xanthogranulomatous cholecystitis.

Discussion
Emphysematous cholecystitis is a variant of acute cholecystitis caused by gas-producing organisms with gas images in the gallbladder and gallbladder wall.Diabetes mellitus, hypertension, and postoperative gastric cancer have been suggested as risk factors for emphysematous cholecystitis.Clostridium spp., including Clostridium perfringens, are the most common organisms causing emphysematous cholecystitis.Early treatment of emphysematous cholecystitis taking Clostridium perfringens into consideration is important, even before the culture results are obtained [2].
Clostridium perfringens is an obligatory anaerobic Gram-positive rod bacterium.It is classified into types A-E according to the toxins produced.Type A is ubiquitous in the human gastrointestinal and urogenital tracts and mainly produces alpha-toxin [3].This alpha-toxin is a lecithinase with phospholipase C activity that degrades phospholipids in cell membranes, causing hemolysis, tissue damage, and vascular endothelial damage.
Bacteremia and septicemia caused by Clostridium perfringens infections are most frequently due to hepatobiliary infections and most often due to mixed infections with Escherichia coli and Klebsiella [4].The uterus and intestinal tract are other sources of infection.The fatality rate is 30%-40% in cases of bacteremia and 70%-100% in cases of sepsis, such as our case [5].Treatment includes penicillin G and clindamycin, polymyxin B-direct hemoperfusion (endotoxin absorption therapy), and treatment of the underlying disease [6].
A literature search was performed in Ichushi and PubMed using the keywords " Clostridium perfringens" and "sepsis."A total of 228 cases were examined, including 227 reported cases published from January 2000 to August 2023 and our case.Among them, 64 cases of hepatobiliary infection were compared based on survival (Table 3   All patients in the survival group and 18 patients in the death group had some form of removal of the infected lesions (p < 0.01).These findings strongly suggest that removal of the infection is a prognostic factor in the treatment of Clostridium perfringens sepsis.Regarding clindamycin, this result may be due to the fact that clindamycin inhibits the production of exotoxins by Clostridium perfringens and other bacterial species [57].The number of cases in both groups was small.Thus, more detailed studies with a larger number of cases are needed.
This study has a limitation.Some of the death cases included in this study were in very poor condition, and the infected lesions could not be removed.However, all patients in the survival group had some form of removal of the infected lesions.We believe that drainage or other forms of removal of infected lesions should be considered regardless of the patients' general conditions to save their lives.

Conclusions
In this study, we reported a case of emphysematous cholecystitis with sepsis caused by Clostridium perfringens.In emphysematous cholecystitis, it is important to start the treatment with Clostridium perfringens in mind.Furthermore, we should actively consider removing infected lesions to save patients' lives.

FIGURE 5 :
FIGURE 5: Abdominal CT scan showed fluid retention where there was originally a gas image of the liver abscess (red arrow).

FIGURE 6 :
FIGURE 6: PTAD (red arrow) was performed by puncture from the side of PTGBD (white arrow).

TABLE 4 : Comparison of the two groups
Of the 64 patients, 22 survived, and 42 died.The median age was 65 (48-79) years in the survival group and 70.5years in the death group (p = 0.16).In the survival group, 15 were males, and 7 were females; in the death group, 31 were males, and 11 were females (p = 0.63).Diabetes mellitus was reported in 12 patients in the survival group and 20 in the death group (p = 0.60).Cancer was reported in 6 patients in the survival group and 11 in the death group (p = 0.93).Clindamycin was used in 8 patients in the survival group and 6 in the death group (p = 0.04).